Objective To observe the effect of Xiaozhihugan(XZHG)capsule on mice with high-fat feed induced non-alcoholic fatty liver disease(NAFLD),and to explore its mechanism based on FXR-SHP pathway.Methods Thirty and six male C57BL/6J mice were randomly divided into 6 groups,which included the Control group,Model group,Yishanfu group(YSF),low-dose Xiaozhihugan capsule group(XZHG-L),medium-dose Xiaozhihugan capsule group(XZHG-M)and high-dose Xiaozhihugan capsule group(XZHG-H).After the successful modeling,the XZHG group and the YSF group were given intervention for 12 weeks.The body weight and liver weight of mice were recorded.The liver pathological conditions were observed by HE staining,and the liver fat infiltration was evaluated by oil red O staining.The biochemical levels of mouse serum were detected by the fully automatic biochemical analyzer.The levels of interleukin(IL)-6 and IL-10 were determined by ELISA.The farnesoid X receptor in liver tissues was detected by Western blot and real-time fluorescence quantitative PCR,respectively,small heterodimer partner(SHP),proteins and mRNA levels of SREPP-1 and cholesterol 7α-hydroxylase(CYP7A1).Results The Model group showed disordered liver cell arrangement and serious fat infiltration.The XZHG-H group significantly improved the liver histopathological changes of NAFLD mice,and the fat infiltration was reduced.After XZHG and YSF intervention,the levels of serum ALT,AST,ALP,TG and TBA decreased(all P<0.05).ELSIA results showed that the level of pro-inflammatory factor IL-6 in the serum and liver tissue of the XZHG-H group was significantly decreased,while the level of anti-inflammatory factor IL-10 was significantly increased.The expression levels of FXR and SHP proteins and mRNA in each dose group of XZHG were significantly increased,while the expression levels of SREPP-1 and CYP7A1 proteins and mRNA were significantly decreased(all P<0.05),and the expressions of FXR and SHP proteins and mRNA in the XZHG-H group were higher than those in the YSF group.FXR and SHP protein and mRNA expressions in XZHG-H group were higher than those in YSF group,while SRBEP-1 and CYP7A1 protein and mRNA expressions were slightly lower than those in YSF group.Conclusion XZHG capsule can improve the arrangement of hepatocytes,the pathological manifestations of lipid deposition,improve liver function and reduce inflammation index through FXR-SHP signaling pathway.

Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.

Objective By observing the clinical efficacy of Zhinao capsule in the treatment of Parkinson's disease with mild cognitive impairment(PD-MCI)patients,we also explored the potential mechanism using network pharmacology and molecular docking technology,with the aim of providing a new idea for the treatment of PD-MCI with traditional Chinese medicine.Methods Random number table method was applied to divide the control group and test group into 35 cases each.Parkinson's disease basic treatment plan was used in the control group,and Zhinao capsule was added in the test group.The observation course was determined to be 8 weeks.The Montreal Cognitive Assessment(MoCA)score,MDS-Unified Parkinson's Disease Rating Scale(MDS-UPDRS)Ⅰ,Ⅱ and Ⅲ,PD Traditional Chinese Medicine(PD-TCM),and safety-related indexes were completed before treatment and at the end of the 8th week of treatment.The network pharmacology method was used to obtain the targets related to Zhinao capsules and PD-MCI.Constructed and analyzed the"drug-component-target"network.Analysis of"drug-disease"intersecting targets and enrichment of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways was obtained using R language.Protein-protein interaction(PPI)networks were constructed using Cytoscape 3.9.1.Finally,molecular docking was conducted.Results The MoCA score of the test group was remarkably greater than that of the control group after treatment(P<0.05);and the TCM syndrome score were noticeably below that of the control group(P<0.05).The test group showed a notable increase in the mean value of MoCA scale scores,and a clear decrease in the MDS-UPDRS Ⅰand PD-TCM before and after treatment(P<0.05).The MDS-UPDRS Ⅱ and Ⅲ scale scores of the test and control groups decreased to different degrees after treatment,but there was no significant difference(P>0.05).Zhinao capsules for PD-MCI treatment has calycosin,quercetin,kaempferol,etc.as core active ingredients,and TNF,IL-1β,IL-6,etc.as core targets.Molecular docking results also showed better binding of the core target to the active ingredient.Zhinao capsules regulates the expression of PPAR,cGMP-PKG,Oxytocin and other signaling pathway-related genes.Conclusion The Zhinao capsules can improve the cognitive function of PD-MCI patients,and the mechanism may be related to the fact that the components such as calycosin,quercetin,and kaempferol act on the targets such as TNF,IL-1β,and IL-6,and mediate the signaling pathways such as PPAR,cGMP-PKG,and Oxytocin.

Objective Exploring the mechanism of mitophagy-mediated efferocytosis in myocardial fibrosis progression based on transcriptomics and bioinformatics,with potential chinese herbal medicine prediction and experimental validation.Methods A rat model of myocardial fibrosis was constructed by injecting angiotensin Ⅱ subcutaneously.RNA extraction and high-throughput sequencing were performed on myocardial tissue of rats,and differentially expressed genes(DEGs)were detected.Efferocytosis-related genes(ERGs)were obtained from the GeneCards database,and the intersection of DEGs and ERGs was mapped using the"venneuler"package in R 4.2.0 software.Differentially expressed efferocytosis-related genes(DEERGs)were obtained,and KEGG and GO enrichment analyses were performed for DEERGs.The network analysis of protein-to-protein interactions(PPI)and identification of key genes of DEERGs and mitochondrial autophagy(PINK1,P62)were conducted.The key genes were imported into Coremine database for chinese herbal medicine prediction.Combined with the Traditional Chinese Medicine pathogenesis of myocardial fibrosis and the previous research progress,the highest frequency of Astragali Radix,Carthami Flos and Lepidii Semen was selected for animal experiments.Masson staining was used to analyze the degree of fibrosis.Mitochondrial swelling assay and mitochondrial membrane potential detection were performed to evaluate the extent of mitochondrial dysfunction.RT-PCR and Western blot were employed to measure the mRNA and protein expression of mitophagy-related genes to assess mitophagy levels.Cardiac-resident macrophages were isolated,treated with AngⅡ,and subsequently assessed for their efferocytosis of apoptotic endothelial cells.Results There were 428 DEGs between in the control group and model group,including 165 up-regulated and 263 down-regulated DEGs.250 ERGs were identified from GeneCards database,and 12 DEERGs were obtained by drawing the intersection of DEGs and ERGs.KEGG and GO enrichment analysis of DEERGs showed that the process involved cellular burial,mitochondrial autophagy and endothelial cell regulation.PPI network analysis and identification of key genes of DEERGs and mitochondrial autophagy(PINK1,P62)were performed.The top 10 key genes were HIF1A,PINK1,GABARAP,ARG1,PPARG,UCP2,SQSTM1,CD36,SIRT1 and RAB7A.The key genes were imported into Coremine database to search for corresponding chinese herbal medicine.The most frequent ones were Astragali Radix,Carthami Flos and Lepidii Semen.Experimental validation demonstrated that the Astragali Radix,Carthami Flos and Lepidii Semen formulation inhibited AngⅡ-induced myocardial fibrosis and improved cardiac function in rats.Notably,it significantly enhanced the efferocytosis of apoptotic endothelial cells by AngⅡ-treated resident macrophages,with the high-dose group showing the most pronounced effect(P<0.05).Mechanistic studies using the high-dose Astragali Radix,Carthami Flos and Lepidii Semen formulation group revealed that,compared to control and model groups,the treatment group exhibited reduced mitophagy and ameliorated mitochondrial dysfunction(P<0.05).Conclusion The Astragali Radix,Carthami Flos and Lepidii Semen formulation may inhibit excessive mitophagy by regulating the expression of PINK1 and P62,promote macrophage efferocytosis,and thereby suppress the formation of myocardial fibrosis.

Rheumatic diseases,as a complex class of chronic immune-mediated disorders,involve interplay among genetics,environment,and immunity in their pathogenesis,which remains incompletely elucidated to date.In recent years,with the advancement of epigenetic research,particularly in the field of RNA modifications,the role of m6 A methylation in rheumatic diseases has increasingly garnered attention.Traditional Chinese medicine(TCM),as the indigenous medical system of China,has accumulated extensive experience in the treatment of rheumatic diseases.This article systematically reviewed the research progress of TCM in treating rheumatic diseases such as rheumatoid arthritis,systemic lupus erythematosus,Sj?gren's syndrome,ankylosing spondylitis,and osteoarthritis,as well as improving bone metabolism abnormalities closely related to rheumatic diseases,through regulating m6 A methylation.The aim is to provide novel insights into the treatment of rheumatic diseases with TCM and to offer theoretical support for the development of related functional drugs.

This paper focuses on the formation of Chinese medicine symptoms in late-life depression(LLD).It delves into an interdisciplinary study that combines interoception and the Chinese medicine concept of'holism of physique and spirit'.LLD,as a common psychiatric disorder,has significant differences in clinical characteristics from younger patients,often manifesting physical discomfort and cognitive impairment.As a key link in the body-brain axis,interoception plays a central role in regulating emotions and behaviors,and its abnormalities are closely related to the development of LLD.The Chinese medicine concept of'holism of physique and spirit'provides a therapeutic perspective that unifies the body and the spirit,emphasizing the interaction between visceral functions and emotional states.Psychological interventions,including cognitive-behavioral therapy and mindfulness meditation,are effective in improving interoception and reducing depressive symptoms.In this study,the relationship between interoception and LLD was analyzed through embodied cognition theory and fMRI technology,and the application of'holism of physique and spirit'in treating late-life depression.The challenges and opportunities of interdisciplinary research in the field of late-life depression is discussed,and future research directions is proposed,aiming to provide more scientific and effective strategies for the prevention,diagnosis,and treatment of LLD.

Diabetic kidney disease(DKD)is one of the common microvascular complications in diabetes mellitus patients,with oedema,proteinuria,and continuous decline in renal function as the main clinical manifestations,and traditional Chinese medicine(TCM)believes that diabetic kidney disease is caused by a deficiency of Qi and Yin,which runs through the whole process of the disease.In recent years,academician Tong Xiaolin's theory of"state-target theory"provides new ideas for the treatment of diabetic nephropathy.The"state"is a general term for the overall manifestation of the patient's condition.The overall manifestation of the condition of diabetic kidney disease is a"state of deficiency and impairment"with Qi and Yin deficiency as the key mechanism of the disease.The"target"refers to the specific symptoms of the disease or abnormal examination results,which are the clinical symptoms and abnormal indicators caused by diabetic kidney disease.Ginseng astragali dihuang soup is effective in the treatment of diabetic nephropathy,and the application of this formula based on the theory of state-target can make the therapeutic effect more significant,achieve the therapeutic effect of supporting positive Qi,replenishing the deficiency and benefiting the loss,and improve the clinical symptoms and the abnormal physicochemical indexes of diabetic nephropathy,and the state-target co-adjustment,which can provide a new way of thinking for the diagnosis and treatment of diabetic nephropathy for the clinicians.

The emergence of generative pre-training transformer(GPT)and large language models(LLMs)has brought transformative applications to the medical field.In traditional Chinese medicine,LLMs offer unique opportunities to address in efficiencies in clinical workflows and improve the patient experience.However,the seprospects have challenges,including data quality,security and privacy,disinformation,ethics,and other issues.This paper systematically elaborates on the application of Large Language Models(LLMs)in Traditional Chinese Medicine(TCM),highlighting their value in improving TCM services,enhancing teaching effectiveness,and optimizing healthcare management processes,while conducting an in-depth analysis of potential technical and ethical challenges during real-world implementation.Preventive measures are necessary to ensure the safe and unbiased use of large language models in TCM clinical practice.We encourage clinicians and researchers to address current challenges and optimize largelanguage models while reducing associated risks.The deployment and implementation of large language models in TCM clinical practice will significantly contribute to the dissemination and development of TCM culture.

An increasing number of studies have shown that there is a close relationship between Alzheimer's disease(AD)and diabetes mellitus(DM).Traditional Chinese medicine holds that"kidney yin deficiency"is the common pathogenesis of these two diseases,while modern medicine believes that their pathogenesis involves abnormal aggregation of amyloid proteins,insulin deficiency and resistance,inflammatory response,oxidative stress,and autophagy,among others.The well-known traditional Chinese medicine formula Liuwei Dihuang Pills plays a significant role in the treatment of these two diseases with the same therapeutic approach.Therefore,this article will explore the connection between Liuwei Dihuang Pills and the treatment of AD and DM from different aspects;analyze the common etiology and pathogenesis of AD and DM,and explain the mechanism of prevention and treatment of Liuwei Dihuang Pills,with the aim of providing new ideas and methods for the integrated traditional and Western medicine prevention and treatment of AD and DM in the future.

Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease caused by excessive lipid accumulation in the liver.Its incidence rate is increasing year by year and has become an increasingly serious public healthy problem.The pathogenesis of NAFLD is complex and has not been fully clarified at present.It is mainly related to multiple factors such as genetics,metabolism,intestinal flora and immune response.In order to explore the medication rules and mechanism of action of traditional Chinese medicine(TCM)in the treatment of NAFLD,and to provide references for the treatment of NAFLD with TCM and the research and development of new drugs,this article summarizes the TCM pathogenesis of NAFLD(such as"phlegm and blood stasis interlacing","liver depression and spleen deficiency",etc.)and modern etiology and pathogenesis(such as insulin resistance,lipid disorder,mitochondrial dysfunction,oxidative stress,etc.).The clinical research and experimental data at home and abroad in recent years were integrated to analyze the pathological process of NAFLD intervention by TCM through multiple targets,including improving insulin resistance and lipid metabolism disorders,inhibiting oxidative stress and mitochondrial dysfunction,etc.TCM has shown unique advantages in the prevention and treatment of NAFLD.However,the depth of its mechanism analysis and the level of clinical research still need to be improved.In the future,it is necessary to deepen the mechanism research by combining multi-omics technology to accelerate the modernization development of TCM.